Millions of women have been treated for or are living with breast cancer, and tens of thousands of women are expected to die from the disease each year. As breast cancer disease remains the second leading cause of cancer death in women (after lung cancer), different types of treatment have been developed including surgery, radiation therapy, chemotherapy and hormone therapy. New types of therapies are also going through development and trials in order to treat this malignant disease. This proposal is to use the breakthrough RNAi technology to develop a multi-targeted therapeutics to treat breast cancer. This proposed study is to take advantage of the HKP carriers with siRNA cocktails targeting three specific genes (EGFR, Raf-1 and mTOR) as an RNAi therapeutic protocol for treatment of breast cancer, and to combine the siRNA cocktail with Avastin to mimic a clinical regimen. The success of this approach will have tremendous scientific and therapeutic impacts for combating breast cancer and many other cancers. PUBLIC HEALTH RELEVANCE: As breast cancer disease remains the second leading cause of cancer death in women (after lung cancer), various types of treatment have been developed including surgery, radiation therapy, chemotherapy and hormone therapy. Using the breakthrough RNAi technology, we are developing a multi-targeted therapeutics to treat breast cancer. This proposed study is to take advantage of the HKP carriers with siRNA cocktails targeting three specific genes as an RNAi therapeutic protocol for treatment of breast cancer, and to combine the siRNA cocktail with Avastin to mimic a clinical regimen. The outcome of the project is expected to be of significant value for the patients and pharmaceutical industry. [unreadable] [unreadable] [unreadable]